This study was supported by the National Institute on Alcohol Abuse and Alcoholism Grant AA 10746, This study was presented in part at the Annual Meeting of the Research Society on Alcoholism in San Francisco, CA, July 19–24, 1997.
Chronic Alcohol Intoxication Attenuates Human Immunodeficiency Virus-1 Glycoprotein 120-Induced Superoxide Anion Release by Isolated Kupffer Cells
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 22, Issue 2, pages 474–480, April 1998
How to Cite
Bautista, A. P. (1998), Chronic Alcohol Intoxication Attenuates Human Immunodeficiency Virus-1 Glycoprotein 120-Induced Superoxide Anion Release by Isolated Kupffer Cells. Alcoholism: Clinical and Experimental Research, 22: 474–480. doi: 10.1111/j.1530-0277.1998.tb03676.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication August 14, 1997; accepted November 13, 1997
- Respiratory Burst;
- Mannosylated-Bovine Serum Albumin;
- Protein Kinase C;
- NADPH Oxidase
This work tests the hypothesis that chronic alcohol intoxication suppresses the microbicidal activity of Kupffer cells by modulating the expression of cell surface receptors associated with respiratory burst and the release of potent microbicidal agents [i.e., reactive oxygen species (ROS)]. Because alcohol is also a potential risk factor in human immunodeficiency virus-1 (HIV-1) infection, this study examines the effect of HIV-1 glycoprotein 120 (gp120)-induced ROS release by isolated Kupffer cells. After 16 weeks of ethanol feeding, Kupffer cells from male Sprague-Dawley rats were isolated and assayed for HIV-1 gp120-induced superoxide release. Fluorescein iso-thiocyanate (FITC)-HIV-I gp120 binding, NADPH oxidase, and protein kinase C activity in Kupffer cells were measured. Results show that HIV-1 gp120 induced the release of superoxide anion in a dose-dependent manner in normal rats. Mannosylated-bovine serum albumin inhibited FITC-HIV-1 gp120-mediated superoxide release in normal Kupffer cells by 85%. Moreover, 83 ± 6% of Kupffer cells were FITC-HIV 1 gp120-positive, whereas <30% were CD4-positive. In alcohol-fed rats, HIV-1 gp120-induced ROS release was reduced by 70% and FITC-HIV-1 gp120 binding (in terms of fluorescence intensity per 106 Kupffer cells) by 44% in Kupffer cells, without any change in percent positive cells for this ligand. Concomitantly, HIV-1 gp120-induced translocation of NADPH oxidase to the plasma membranes of Kupffer cells in alcohol-fed rats was suppressed by 60%. In contrast, alcohol consumption significantly increased total protein kinase C activity and phorbol ester-induced superoxide release by Kupffer cells. These studies demonstrate that Kupffer cells are likely targets of HIV-1 whose binding sites on macrophages could also include mannose-specific receptors. These observations further suggest that suppression of HIV-1 gp120-mediated ROS production in chronic alcoholics is due to altered cell surface receptor expression for gp120, and defective postreceptor signaling mechanisms, which in turn could lead to attenuated microbicidal activity of hepatic macrophages.